Light-activatable liposomes for repetitive on-demand drug release and immunopotentiation in hypoxic tumor therapy

Yuanyuan Yang; Xin Liu; Wen Ma; Qing Xu; Gui Chen; Yufei Wang; Haihua Xiao; Nan Li; Xing-Jie Liang; Meng Yu; Zhiqiang Yu

doi:10.1016/j.biomaterials.2020.120456

Light-activatable liposomes for repetitive on-demand drug release and immunopotentiation in hypoxic tumor therapy

Biomaterials. 2021 Jan:265:120456. doi: 10.1016/j.biomaterials.2020.120456. Epub 2020 Oct 15.

Authors

Yuanyuan Yang¹, Xin Liu², Wen Ma¹, Qing Xu¹, Gui Chen¹, Yufei Wang³, Haihua Xiao⁴, Nan Li⁵, Xing-Jie Liang⁶, Meng Yu⁷, Zhiqiang Yu⁸

Affiliations

¹ Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
² Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China; Department of Pharmacy, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Foshan, 528300, China.
³ CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, 100190, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
⁴ Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
⁵ Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China.
⁶ CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, 100190, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: liangxj@nanoctr.cn.
⁷ Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. Electronic address: yumeng999@smu.edu.cn.
⁸ Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. Electronic address: yuzq@smu.edu.cn.

PMID: 33099066
DOI: 10.1016/j.biomaterials.2020.120456

Abstract

External stimuli-responsive nanomedicine with desirable repetitive on-demand drug release character is postulated to greatly accommodate patients' flexible medication regime. To this object, light-activatable liposomes (Pt/Ce6-LP) integrated with both a Ce6 photodynamic component and a tetravalent platinum prodrug (Pt(IV)) chemotherapeutic component are engineered. This multifunctional system was rationally designed using unsaturated phospholipid to achieve repetitive on-demand drug release under discontinuous light irradiation, thus performing chemo-photodynamic therapy effect and immunopotentiation in hypoxic tumor. Furthermore, glutathione (GSH) consumption during transformation from Pt(IV) prodrug to Pt(II) can avoid depletion of reactive oxygen species (ROS) in photodynamic therapy (PDT). Note this positive feedback loop appears to remodel the redox balance of H₂O₂ and GSH in tumors, alleviating the hypoxic tumor microenvironment. The alleviated hypoxia is found to be critical to the enhancement of PDT efficacy, reversal of cisplatin resistance in tumors, and polarization of tumor-associated macrophages (TAMs) to the immunocompetent M1-phynotype. Pt/Ce6-LP with light radiation demonstrates significant antitumor effect and persistent post-medication inhibition in patient-derived tumor xenograft model of hepatocellular carcinoma.

Keywords: Hypoxia alleviation; Immunopotentiation; Light-activatable liposomes; Oxidative equilibrium; Repetitive drug release.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Drug Liberation
Humans
Hydrogen Peroxide
Hypoxia / drug therapy
Liposomes*
Photochemotherapy*
Photosensitizing Agents / therapeutic use

Substances

Liposomes
Photosensitizing Agents
Hydrogen Peroxide